Schistosomiasis is a major neglected tropical disease of public health concern to a billion people with 200 million currently infected and 779 million at risk to acquire the infection, the majority of these in Africa. The disease has a high impact on affected people's lives with disability adjusted life years at 70 million years which rank this malady ahead of malaria. Current control strategies have been geared toward repeated with a drug discovered in the 1970s and standards for monitoring administration and progress have been inconsistent and inadequate. Reliance on the drug therapy approach alone is a poor strategy since this approach has had little impact on the reduction of disease transmission and there is always the inherent threat of drug resistance being developed by the parasite. A prophylactic schistosomiasis vaccine that provides at least 50% protection would play an important role in dramatically reducing the impact of this disease. Vaccine-generated immune responses could lead to reduced worm burdens and lower egg production and ultimately result in lower transmission. This application is an extension of our systematic and methodical approach towards developing a vaccine for schistosomiasis. Over the last twenty years, we have applied this strategy towards developing Sm-p80 into a viable vaccine candidate. At present, to our knowledge, Sm- p80 is the sole schistosome vaccine candidate that has been tested for prevention, interruption of transmission and in therapy. Our candidate vaccine has three protective effects: worm reduction, egg reduction, and protection against acute disease. Funding this application will help our continuing efforts to develop Sm-p80 towards manufacture for future human clinical trials, ultimately resulting in an approved vaccine.